1. Field of the Invention
This invention relates generally to bacteria as a source of therapeutic compounds and, more particularly, to a new marine actinomycete taxon and to therapeutic compounds derived therefrom.
2. Background
Pharmaceutical researchers have long tapped actinomycetes, gram-positive, soil bacteria with fungal-like filaments, as a source of novel antibiotics and antitumor compounds. In addition, pharmaceutical researchers have long been using natural antibiotics from actinomycetes as models and starting materials for the production of new medicines. Prominent examples are the antibiotics actinomycin, streptomycin, and vancomycin. The repertoire of these microorganisms, previously known to live mainly in soil, has by now been well studied. Approximately 120 drugs have their origins in terrestrial actinomycetes, and although highly prolific for more than 50 years, the chemical diversity from this source began to decline more than 10 years ago.
Marine actinomycetes have only recently been discovered. Like their terrestrial relatives, these organisms make some highly biologically active substances. A U.S. team has recently discovered a new antitumor agent in one of these marine bacteria. The compound salinosporamide A, is a potent inhibitor of several types of human cancers. This compound is produced by marine actinomycete strain CNB-392, a member of this new bacterial genus called “Salinospora.” Salinospora strains have been recovered from muddy sediments collected at depths in excess of 1,000 meters from the Atlantic and Pacific Oceans, the Red Sea, and the Gulf of California. At this depth, there is no light, very high pressure, and low temperature.
New methods have also been developed for sifting through the samples (which contain roughly one billion microorganisms per cubic centimeter), identifying specific microorganisms by genetic methods and screening their metabolic products for anticancer and antibiotic properties. From 100 strains of Salinospora preliminarily tested, 80% produced molecules that inhibit cancer cell growth and roughly 35% revealed the ability to kill pathogenic bacteria and fungi. Salinosporamide A, is a powerful inhibitor of certain colon and lung and breast cancers, and it has been shown to act by the inhibition of the intracellular proteasome.
However, culture of marine organisms has proven difficult in the laboratory. A number of explanations have been proposed to explain this phenomenon. From an eco-physiological point of view, it has been argued that there exist obligate oligotrophs that cannot grow in any nutrient rich media, such as is commonly used to grow land bacteria. It has even been proposed that sudden exposure to nutrient rich external conditions induces suicide responses originating from an imbalance between anabolism and catabolism. Thus there is a need in the art for improved methods for isolating and culturing marine bacteria, such as actinomycetes.
Antibiotic resistance of pathogenic bacteria, including pathogenic actinobacteria, such as Mycobacterium tuberculosis, is a well-known problem faced by medical practitioners in treatment of bacterial diseases. Therefore, there is a further need in the art for new antibiotics and drugs effective to circumvent resistance to existing antibiotics in treatment of bacterial infections in humans and in other mammals, including domestic and farm animals.
Many types of cancer cells also exhibit drug resistance. Accordingly, there is also an urgent need for new anticancer agents, for example, those with new pharmacological properties and unusual structures that may be found.